Prostate cancer is one of the most frequently diagnosed neoplasms in American men. Few candidate regulatory genes have been found to play roles in prostate morphogenesis, and the complex genetic mechanisms that underlie the progression from normal prostatic growth to adenocarcinoma are largely unknown. The NIcc-3. I gene encodes a homeodomain transcription factor that is expressed during early prostate development and in the epithelial cells of the adult gland. Although the biochemical function of Nkx-3. 1 is not well defined, it is suggested to play a pivotal role in prostate morphogenesis and maintenance. In humans, Nkx-3.1 maps to 8p2 1, a chromosomal region that is frequently deleted in human tumors. We propose that loss of N/ax-3. 1 expression plays a causal role in prostate tumorigenesis. This hypothesis will be tested using both human prostate tissue and transgenic mice to examine N/cx-3.1 expression normal development and tumorigenesis.